The unifying aim of VIROMARKERS is to define virus related biomarkers to improve management of chronic diseases, including biomarkers of response to antiviral treatment of persistent viral infections and virome features as indicators of disease progression in immunosuppressed people. The project has the following objectives: 1. To demonstrate a novel bioinformatics method for prediction of HIV-1 susceptibility to broadly neutralising antibodies based on the HIV-1 gp120 sequence. 2. To demonstrate novel HDV biomarkers (HDV-RNA, HBsAg isoforms and HDV genotype) to predict treatment response to the recently approved anti-HDV bulevirtide. 3. To validate serum CMV-RNA as a biomarker of CMV infection/reactivation to optimise the correct timing for preventive strategies in patients undergoing hematopoietic stem cell transplantation. 4. To validate the torque teno virus DNA as a prognostic biomarker for CMV disease in immunocompromised patients. 5. To validate total and intact cellular HIV DNA as a biomarker of HIV infection status to guide novel antiviral strategies. Validation or demonstration of several technologies required to measure the candidate biomarkers is an integral part of the project objectives. In particular, this refers to the following diagnostic tools: • dPCR as a tool for HDV quantification • NGS platform for HDV sequencing • qPCR diagnostics for CMV-RNA quantification • IPDA suitable for detection of intact HIV-DNA in any viral subtype • qPCR diagnostics for TTV-DNA Leveraging on the regulatory expertise present in the consortium, VIROMARKERS will define the regulatory pathway for each of its outcomes and will generate the experimental data necessary to move prototype methods and tools to regulatory approval. Overall, VIROMARKERS, with its public private partnership nature, will make available for healthcare providers and for researchers robust and fit-for-purpose biomarkers and linked technologies enabling their clinical use in response to important unmet clinical needs with, in the end, an important impact also for patients. VIROMARKERS is supported by the Innovative Health Initiative Joint Undertaking (IHI JU). The JU receives support from the European Union’s Horizon Europe research and innovation programme and COCIR, EFPIA, Europa Bío, MedTech Europe, and Vaccines Europe

The EuCARE project gathers a comprehensive multidisciplinary team of clinicians, virologists, epidemiologists, statisticians and top experts in artificial intelligence to unveil the impact of SARS-CoV-2 variants on key sectors of public health, as addressed by the call. The specific activities include: 1. The assessment of natural and artificial immunity to the different viral variants in health care workers with the aim of defining the cross-immunization patterns and the risk of vaccine escape, informing vaccination strategies for the general population; 2. The analysis of the clinical course and long-term follow-up of hospitalized COVID-19 patients to derive the role of different viral variants in the outcome of the infection, including post-acute sequelae of SARS-CoV-2 infection; 3. The definition of the best strategies to control the spread of different viral variants in schools, by comparing the outcome of diverse containment and prevention measures in relation to the prevalence and dynamics of the variants. To ensure a suitable representativeness of the different variants, vaccines and preventive measures, EuCARE has secured the appropriate cohorts from diverse geographic areas including European countries, Kenya, Mexico, Russia and Vietnam, and will consolidate or expand interactions with other cohorts. To deal with complex interactions among many variables, including large dimensional parameters, EuCARE harnesses the power of artificial intelligence to define the role of viral variants and inform clinical guidelines and prevention measures. In the longer-term, EuCARE is committed to maintain active cooperation beyond the duration of the project with a dedicated task in the project. The solid IT and ethics infrastructure and the harmonised research procedures will make the cohort and laboratory network rapidly available to tackle newly emerging infectious diseases, thus contributing to pandemic preparedness on a global scale.